Markers of positive affect and brain state synchrony discriminate melancholic from non-melancholic depression using naturalistic stimuli

• Published in: Molecular psychiatry 2024-08
• Main Authors: Mosley, Philip E, van der Meer, Johan N, Hamilton, Lachlan H W, Fripp, Jurgen, Parker, Stephen, Jeganathan, Jayson, Breakspear, Michael, Parker, Richard, Holland, Rebecca, Mitchell, Brittany L, Byrne, Enda, Hickie, Ian B, Medland, Sarah E, Martin, Nicholas G, Cocchi, Luca
• Format: Article
• Language: English
• ISSN: 1476-5578; 1476-5578
• DOI: 10.1038/s41380-024-02699-y

Melancholia has been proposed as a qualitatively distinct depressive subtype associated with a characteristic symptom profile (psychomotor retardation, profound anhedonia) and a better response to biological therapies. Existing work has suggested that individuals with melancholia are blunted in their display of positive emotions and differ in their neural response to emotionally evocative stimuli. Here, we unify these brain and behavioural findings amongst a carefully phenotyped group of seventy depressed participants, drawn from an established Australian database (the Australian Genetics of Depression Study) and further enriched for melancholia (high ratings of psychomotor retardation and anhedonia). Melancholic (n = 30) or non-melancholic status (n = 40) was defined using a semi-structured interview (the Sydney Melancholia Prototype Index). Complex facial expressions were captured whilst participants watched a movie clip of a comedian and classified using a machine learning algorithm. Subsequently, the dynamics of sequential changes in brain activity were modelled during the viewing of an emotionally evocative movie in the MRI scanner. We found a quantitative reduction in positive facial expressivity amongst participants with melancholia, combined with differences in the synchronous expression of brain states during positive epochs of the movie. In non-melancholic depression, the display of positive affect was inversely related to the activity of cerebellar regions implicated in the processing of affect. However, this relationship was reduced in those with a melancholic phenotype. Our multimodal findings show differences in evaluative and motoric domains between melancholic and non-melancholic depression through engagement in ecologically valid tasks that evoke positive emotion. These findings provide new markers to stratify depression and an opportunity to support the development of targeted interventions.